The .beta.-lactam halide compound of the invention represented by the general formula (2) is prepared by reacting halogen molecules with an allenyl .beta.-lactam compound represented by the general formula (3) as is already known (Can. J. Chem., 1978, 56, 1335). However, this process affords a mixture of .alpha., .beta.- and .beta., .gamma.-position isomers depending on the kind of halogen molecule and is not usable in actuality. This process further gives the product via an unstable allene compound as an intermediate and therefore involves many problems on an industrial scale. ##STR2## wherein R.sup.1 and R.sup.3 are as defined below, and R.sup.5 is lower alkyl.
It is also reported that as shown in the diagram, a keto-form .beta.-lactam compound is enolized into an enol ether or vinyl halide, followed by halogenation with N-bromosuccinimide (NBS) or N-chlorosuccinimide (NCS) in the presence of a radical generating agent (JP-A-135859/1983). Since this process requires use of a hazardous reagent for reaction, processes which are industrially more feasible are desired. ##STR3## wherein R.sup.6 is phthalimido, aryloxyalkaneamido or alkanoyl, R.sup.7 is thiocyanato, alkanoyl, arylthio, benzothiazolethio, or alkoxycarbonyl which may be substituted with alkoxyl, cycloalkyl or the like, R.sup.8 is alkyl which may be substituted with a halogen, aryl or the like, X is chlorine or the like, and Y is a halogen atom.
Further a process is already known for preparing the exo-methylenepenam compound of the invention which is represented by the general formula (5), by the decarboxylation Pummerer-type transition reaction of penam-2-carboxylic acid derived from penicillin as illustrated in Diagram (A) (Bawldwin et al., J. Chem. Soc., Chem. Commun., 1987, 81), whereas this process comprises as many as eight reaction steps, and is as low as up to 6% in overall yield and by no means feasible.
Diagram (A) ##STR4##
Also known are a synthesis process wherein an allenyl .beta.-lactam compound obtained from penicillin is subjected to acid hydrolysis, followed by intramolecular cyclization (S. Torii et al., Tetrahedron Lett., 1991, 32, 7445) as shown in Diagram (B), and a synthesis process wherein an allenyl .beta.-lactam compound is subjected to a reductive cyclization reaction (S. Torri et al., Synlett., 1992, 878, S. Torri et al., Chemistry Express, 1992, 7, 885, J. Chem. Soc., Chem. Commun., 1992, 1793). These processes nevertheless have various problems such as cumbersomeness of the reaction procedure for industrial operation since the reaction is conducted via an unstable allene compound as an intermediate.
Diagram (B) ##STR5##
An object of the present invention is to provide a process adapted to produce a .beta.-lactam halide compound represented by the general formula (2) from a .beta.-lactam halide compound represented by the general formula (1) and readily available industrially, in a high yield with a high purity through a safe and simplified procedure, the process being developed by realizing milder conditions for effecting halogenation and a reaction for introducing the leaving group.
Another object of the invention is to provide a process adapted to produce an exo-methylenepenam compound of the general formula (5) from the .beta.-lactam halide compound of the general formula (2) in a high yield with a high purity through a safe and simplified procedure by developing a novel metal reduction system and a novel electrolytic reduction system and thereby effecting allenization and conversion to an exo-methylenepenam at the same time efficiently.